Evidence mapPaperPMID 39359253Full record

ArticleFrontiers in pharmacology2024

Activation of AMPK/SIRT1/FOXO3a signaling by BMS-477118 (saxagliptin) mitigates chronic colitis in rats: uncovering new anti-inflammatory and antifibrotic roles.

Elsayed A Elmorsy, Mahmoud E Youssef, Mohamed R Abdel-Hamed, Maha M Amer, Sahar R Elghandour, Abdullah S Alkhamiss, Nahla B Mohamed, Mostafa M Khodeir, Hossam A Elsisi, Thamir Saad Alsaeed and 4 more

Abstract read
In one paragraph

Article in Frontiers in pharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Elsayed A ElmorsyDepartment of Pharmacology and Therapeutics, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
Mahmoud E YoussefDepartment of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt.
Mohamed R Abdel-HamedDepartment of Anatomy, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
Maha M AmerDepartment of Anatomy, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
Sahar R ElghandourDepartment of Anatomy and Histology, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
Abdullah S AlkhamissDepartment of Pathology, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
Nahla B MohamedDepartment of Pathology, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
Mostafa M KhodeirDepartment of Pathology, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
Hossam A ElsisiDepartment of Pharmacology and Toxicology, College of Pharmacy, Qassim University, Buraidah, Saudi Arabia.
Thamir Saad AlsaeedDepartment of Biology and Immunology, College of Medicine, Qassim University, Buraidah, Saudi Arabia.
Manal M KamalDepartment of Medical Physiology, Faculty of Medicine, Assiut University, Assiut, Egypt.
Abousree T EllethyDepartment of Oral and Medical Basic Sciences, Biochemistry Division, College of Dentistry, Qassim University, Buraidah, Saudi Arabia.
Basem H ElesawyDepartment of Pathology, College of Medicine, Taif University, Taif, Saudi Arabia.
Sameh SaberDepartment of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, Egypt.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Ulcerative colitis (UC) is a debilitating chronic disease marked by persistent inflammation and intestinal fibrosis. Despite the availability of various treatments, many patients fail to achieve long-term remission, underscoring a significant unmet therapeutic need. BMS-477118, a reversible inhibitor of dipeptidyl peptidase 4 (DPP4), has demonstrated anti-inflammatory properties in preclinical and clinical studies with minimal adverse effects compared to other antidiabetic agents. However, the potential benefits of BMS-477118 in chronic UC have not yet been explored. In this study, we aimed to investigate the effects of BMS-477118 in rats subjected to chronic dextran sodium sulfate (DSS) administration. Our findings indicate that BMS-477118 activates the interconnected positive feedback loop involving AMPK, SIRT1, and FOXO3a, improving histological appearance in injured rat colons. BMS-477118 also reduced fibrotic changes associated with the chronic nature of the animal model, alleviated macroscopic damage and disease severity, and improved the colon weight-to-length ratio. Additionally, BMS-477118 prevented DSS-induced weight loss and enhanced tight junction proteins. These effects, in conjunction with reduced oxidative stress and its potential anti-inflammatory, antiapoptotic, and autophagy-inducing properties, fostered prolonged survival in rats with chronic UC. To conclude, BMS-477118 has the potential to activate the AMPK/SIRT1/FOXO3a signaling pathway in inflamed colons. These results suggest that the AMPK/SIRT1/FOXO3a pathway could be a new therapeutic target for UC. Further research is mandatory to explore the therapeutic possibilities of this pathway. Additionally, continued studies on the therapeutic potential of BMS-477118 and other DPP4 inhibitors are promising for creating new treatments for various conditions, including UC in diabetic patients.

Indexed as

AMPK/SIRT1/FOXO3aBMS-477118 (saxagliptin)chronic ulcerative colitisDPP4 inhibitorsintestinal inflammation/fibrosisnovel therapeutic target

Identifiers

PMID39359253
PMCPMC11445602

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.